Qu Zihao, Huang Jiawei, Yang Fangkun, Hong Jianqiao, Wang Wei, Yan Shigui
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310009, Hangzhou, China.
Orthopedic Research Institute of Zhejiang University, Zhejiang, 310009, Hangzhou, China.
Arthritis Res Ther. 2020 May 18;22(1):118. doi: 10.1186/s13075-020-02202-2.
Sex hormone-binding globulin (SHBG) has been reported to be a risk factor associated with the development of arthritis by previous observational studies more so of three common forms of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). This study aimed to determine whether the concentrations of circulating SHBG are causally associated with the risk of OA, RA, and AS.
The two-sample Mendelian randomization (MR) approach was used for this study. The inverse-variance-weighted (IVW) method was used for the main analysis. Single-nucleotide polymorphisms (SNPs) associated with SHBG were selected from a large genome-wide association study (GWAS) of 28,837 European individuals. The summary statistics for OA, RA, and AS were extracted from the UK Biobank Resource (n = 361,141) and a GWAS dataset (n = 455,221).
Positive causal associations were found between circulating SHBG concentrations and OA (effect = 1.086; 95% CI, 1.009 to 1.168; P = 0.027) and RA (effect = 1.003; 95% CI, 1.000 to 1.007; P = 0.047) in overall analyses. However, there was no evidence of association between SHBG levels and AS. Based on the stratification of skeletal sites, SHBG levels were found to be significantly associated with hip OA (effect = 1.423; 95% CI, 1.219 to 1.660; P = 7.753 × 10). However, this was not the case with knee OA.
There were positive causal effects of circulating SHBG on the development of OA and RA. Moreover, there was a site-specific association between SHBG and hip OA. Evidently, measurement of SHBG in serum could be valuable in the clinical assessment of arthritis especially in early screening and prevention of OA and RA. However, the mechanisms by which SHBG plays causal roles in the development of arthritis require further investigations.
既往观察性研究报告称，性激素结合球蛋白（SHBG）是与三种常见关节炎（骨关节炎（OA）、类风湿关节炎（RA）和强直性脊柱炎（AS））发病相关的危险因素。本研究旨在确定循环SHBG浓度是否与OA、RA和AS的发病风险存在因果关系。
本研究采用两样本孟德尔随机化（MR）方法。主要分析采用逆方差加权（IVW）法。从一项对28837名欧洲个体进行的大型全基因组关联研究（GWAS）中选择与SHBG相关的单核苷酸多态性（SNP）。OA、RA和AS的汇总统计数据从英国生物银行资源库（n = 361141）和一个GWAS数据集（n = 455221）中提取。
在总体分析中，发现循环SHBG浓度与OA（效应 = 1.086；95%置信区间，1.009至1.168；P = 0.027）和RA（效应 = 1.003；95%置信区间，1.000至1.007；P = 0.047）之间存在正因果关联。然而，没有证据表明SHBG水平与AS之间存在关联。基于骨骼部位分层，发现SHBG水平与髋部OA显著相关（效应 = 1.423；95%置信区间，1.219至1.660；P = 7.753×10）。然而，膝部OA并非如此。
循环SHBG对OA和RA的发病有正向因果作用。此外，SHBG与髋部OA之间存在部位特异性关联。显然，血清中SHBG的检测在关节炎的临床评估中可能具有重要价值，尤其是在OA和RA的早期筛查和预防中。然而，SHBG在关节炎发病中发挥因果作用的机制需要进一步研究。
